Several factors that predict the outcome of large B‐cell lymphoma patients who relapse/progress after chimeric antigen receptor (CAR) T‐cell therapy can be identified before cell administration

Abstract Aim The aim of this study was to analyse the outcomes of patients with large B‐cell lymphoma (LBCL) treated with chimeric antigen receptor T‐cell therapy (CAR‐Tx), with a focus on outcomes after CAR T‐cell failure, and to define the risk factors for rapid progression and further treatment. Methods We analysed 107 patients with LBCL from the Czech Republic and Slovakia who were treated in ≥3rd‐line with tisagenlecleucel or axicabtagene ciloleucel between 2019 and 2022. Results The overall response rate (ORR) was 60%, with a 50% complete response (CR) rate. The median progression‐free survival (PFS) and overall survival (OS) were 4.3 and 26.4 months, respectively. Sixty‐three patients (59%) were refractory or relapsed after CAR‐Tx. Of these patients, 39 received radiotherapy or systemic therapy, with an ORR of 22% (CR 8%). The median follow‐up of surviving patients in whom treatment failed was 10.6 months. Several factors predicting further treatment administration and outcomes were present even before CAR‐Tx. Risk factors for not receiving further therapy after CAR‐Tx failure were high lactate dehydrogenase (LDH) levels before apheresis, extranodal involvement (EN), high ferritin levels before lymphodepletion (LD) and ECOG PS >1 at R/P. The median OS‐2 (from R/P after CAR‐Tx) was 6.7 months (6‐month 57.9%) for treated patients and 0.4 months (6‐month 4.2%) for untreated patients (p < 0.001). The median PFS‐2 (from R/P after CAR‐Tx) was 3.2 months (6‐month 28.5%) for treated patients. The risk factors for a shorter PFS‐2 (n = 39) included: CRP > limit of the normal range (LNR) before LD, albumin < LNR and ECOG PS > 1 at R/P. All these factors, together with LDH > LNR before LD and EN involvement at R/P, predicted OS‐2 for treated patients. Conclusion Our findings allow better stratification of CAR‐Tx candidates and stress the need for a proactive approach (earlier restaging, intervention after partial remission achievement).


| INTRODUCTION
][6][7][8][9][10] CAR T-cells expressing an anti-CD19 CAR have been tested in heavily (≥2 lines of treatment) pretreated DLBCL patients, with encouraging results.2][13][14][15][16] With these successes in mind, we still need to acknowledge that the majority of patients treated with CAR-Tx are not cured, and the prognosis of patients who progress after this therapy is very poor (median overall survival [OS] 5-6 months). 17herefore, we need to enhance the efficacy of CAR-Tx, develop tools to predict treatment failure and identify effective treatments for progressing patients.][20] Patient-related factors include Eastern Cooperative Oncology Group Performance Status (ECOG PS), comorbidities, inflammatory status (C-reactive protein [CRP], ferritin, interleukin-6) and nutritional markers (albumin).4][35][36][37][38] Previous treatment, especially treatment with bendamustine, can negatively affect the input material and final product quality. 391][42] We need to expand upon the limited data on the predictive value of various risk factors for CAR T-cell failure, and we need to better define the optimal

Results:
The overall response rate (ORR) was 60%, with a 50% complete response (CR) rate.The median progression-free survival (PFS) and overall survival (OS) were 4.3 and 26.4 months, respectively.Sixty-three patients (59%) were refractory or relapsed after CAR-Tx.Of these patients, 39 received radiotherapy or systemic therapy, with an ORR of 22% (CR 8%).The median follow-up of surviving patients in whom treatment failed was 10.6 months.Several factors predicting further treatment administration and outcomes were present even before CAR-Tx.Risk factors for not receiving further therapy after CAR-Tx failure were high lactate dehydrogenase (LDH) levels before apheresis, extranodal involvement (EN), high ferritin levels before lymphodepletion (LD) and ECOG PS >1 at R/P.The median OS-2 (from R/P after CAR-Tx) was 6.7 months (6-month 57.9%) for treated patients and 0.4 months (6-month 4.2%) for untreated patients (p < 0.001).
The median PFS-2 (from R/P after CAR-Tx) was 3.2 months (6-month 28.5%) for treated patients.The risk factors for a shorter PFS-2 (n = 39) included: CRP > limit of the normal range (LNR) before LD, albumin < LNR and ECOG PS > 1 at R/P.All these factors, together with LDH > LNR before LD and EN involvement at R/P, predicted OS-2 for treated patients.

Conclusion:
Our findings allow better stratification of CAR-Tx candidates and stress the need for a proactive approach (earlier restaging, intervention after partial remission achievement).

K E Y W O R D S
CAR T-cell failure, outcomes of patients after CAR T-cell therapy failure, relapsed/refractory large B-cell lymphoma, risk factors for CAR T-cell therapy failure management of progression.Our goal was to detect the failure of CAR-Tx and deliver the appropriate treatment as soon as possible.Therefore, the aims of our study were as follows: 1. To analyse the outcomes of LBCL patients after CAR-Tx with a focus on CAR T-cell failure patients.2. To define the risk factors for rapid progressive disease after CAR-Tx that will limit one's ability to receive further active treatment.

| PATIENTS
Since 2019, anti-CD19 CAR-Tx has been used as a treatment modality for R/R LBCL patients after ≥2 lines of treatment in the Czech Republic.All patients ≥18 years with R/R aggressive LBCL after ≥2 lines of treatment who were treated with anti-CD19 commercial products (tisagenlecleucel [tisacel], axicabtagene ciloleucel [axicel]), and those who failed on this therapy from December 2019 to December 2022 were included in this analysis.Patients from Slovakia who were treated in the Czech Republic before CAR-Tx was available in their country were also included, resulting in a total of 107 patients.Thirty one (29%) patients were heavily pretreated (≥4 lines of therapy for LBCL before apheresis for CAR-Tx).The data were retrospectively collected from the electronic medical records of each institution through chart review by the individual investigators.

| METHODS
The histological diagnosis of aggressive LBCL was established according to the World Health Organisation Classification criteria of 2008. 43Chimeric antigen receptor T-cell failure was defined as the best response of either stable disease or progression, relapse from complete remission, or progression after a best response of partial remission.Data on parameters at the time of apheresis (APH), before lymphodepletion (LD) and at the time of relapse/progression (R/P) were collected:

| At the time of apheresis (APH)
Histological subtype of LBCL, age at APH, presence of the 'bulky disease' (≥5 cm) at APH, ECOG PS at APH, level of LDH at APH, presence of extranodal (EN)/ central nervous system (CNS) involvement at APH; number of treatment lines before APH and bendamustine pretreatment.

| Before lymphodepletion (LD)
LDH, ECOG PS, 'bulky disease' (≥5 cm), EN/CNS involvement, CRP, albumin and full blood count parameters, including lymphocyte count, the value of ferritin just before LD and on the day of CAR T-cell administration (D0), the International Prognostic Index (IPI) + age-adjusted (AA) IPI and the type of bridging therapy.We analysed the type of LD agent and available CAR T-cell peak expansion data after CAR-Tx.

| At the time of R/P after CAR T-cell failure
Whether a new biopsy of the tumour was taken, whether CD19 antigen was found in the biopsy, persistence of CAR T-cells, 'bulky disease' (≥5 cm), ECOG PS, assessment of LDH and albumin values, EN/CNS involvement, clinical stage III-IV and IPI/AA IPI.
Lymphodepleting regimens were used as described in original publications. 11,125][46] Treatment response was evaluated according to institutional standards (PET/CT or CT examination).The best treatment response after CAR-Tx was documented.The median follow-up was evaluated among surviving (the whole group and the subgroup with R/P after CAR-Tx).
For the detection of CAR T-cells in peripheral blood, a multicolour flow cytometry panel was used.For surface staining of T cells and their subpopulations, the following monoclonal antibodies were used: anti-CD4 peridininchlorophyll-protein complex-cyanine (5.5), anti-CD19 R-phycoerythrin-cyanine7, anti-CD3 allophycocyanin, anti-CD8 allophycocyanin-cyanine7, anti-CD20 pacific blue and anti-CD45 pacific orange.Then, an anti-FMC63 scFv antibody (ACROBiosystems, Newark, DE, USA) conjugated with R-phycoerythrin was used to detect of CAR T-cells.
To calculate the survival of R/P patients after CAR-Tx, we evaluated overall survival-2 (OS-2) (defined below) in the whole group (n = 63), in treated patients (n = 39, OS treated-2) and in untreated patients (n = 24, OSuntreated-2).Progression-free survival-2 (PFS-2) (defined below) was evaluated only in treated patients (PFS treated-2) because in untreated subjects, the date of the PFS-2 event was the same as the date of progression after CAR-Tx.The database was locked for the last follow-up in August 2023.The study adhered to the Declaration of Helsinki.

| STATISTICS
The data were analysed using the statistical software NCSS 2021 (NCSS, LLC, Kaysville, Utah, USA, ncss.com/ softw are/ ncs) and MedCalc software (Mariakerke, Belgium).Overall survival (OS) and progression-free survival (PFS) curves were estimated with the Kaplan-Meier method, and differences were compared by the stratified log-rank test.
Progression-free survival was defined as the time from CAR T-cell infusion (day 0) until the first R/P disease or death from any cause.OS was defined as the time from CAR T-cell infusion (day 0) to documented death from any cause.OS-2 was defined as the time from the diagnosis of R/P after CAR-Tx to documented death from any cause.OS treated-2 was defined as the time from diagnosis of R/P after CAR T-cell infusion to documented death from any cause in patients who received active treatment for R/P after CAR-Tx.PFS treated-2 was defined as the time from R/P after CAR-Tx to the second R/P after CAR-Tx or death from any cause in patients who were treated for R/P after CAR-Tx.Fisher's exact test was used to analyse differences between groups for categorical variables.The Mann-Whitney test was used for quantitative variables.Multivariate analysis was performed by Cox regression analysis using the hierarchic forward stepwise selection process.Multivariate logistic regression was used to identify risk factors for failure to undergo treatment at R/P after CAR T-cell therapy.All point estimates are presented with an appropriate 95% confidence interval.The level of significance was α = 0.05.All p values were two-sided.

| Patient characteristics
Overall, 107 patients were analysed from 11 haematooncology centres: 64 patients with de novo DLBCL, 18 patients with transformed DLBCL, 13 patients with highgrade LBCL and 12 patients with primary mediastinal LBCL (PMBCL).These patients were treated at five centres certified for CAR-Tx.Tisa-cel was administered to 77 patients (72%), and axi-cel was administered to 30 patients (28%).Their basic characteristics are summarised in Table 1.

| Treatment response and clinical outcome after CAR T-cell therapy
The best ORR and CR rate were 60% (n = 64) and 50% (n = 53), respectively.The median follow-up was 17.8 months (range 2.1-44.6)for surviving patients.Among the eleven patients who achieved the best response to PR after CAR-Tx, 10 progressed.Fifty patients died: 45 due to progressive disease (PD), three due to infectious complications, one from other causes and one from unknown causes.The median PFS (Figure 1) and OS were 4.3 months (95% CI 3.1-11.8)and 26.4 months (95% CI 9.5-29.8),respectively, in all patients.The estimated 6-month PFS and OS were 47% and 66%, respectively, and the estimated 12-month PFS and OS were 41% and 56%, respectively.The results of univariate and multivariate Cox regression analyses for PFS and OS are shown in Table 2.In contrast to 'bulky disease' (≥5 cm), the response to bridging therapy lost its predictive value in multivariate analysis for OS/PFS, probably due to the small number of patients.The histological type and poor ECOG PS were not predictive of OS in the multivariate analysis, while an PD 0 (0) 35 (52)   Abbreviations: CR, complete remission; DLBCL, diffuse large B-cell lymphoma; HGBCL, high grade B-cell lymphoma; LNR, limit of normal range; n, number; PD, progressive disease; PMBCL, primary mediastinal B-cell lymphoma; PR, partial remission; SD, stable disease; tDLBCL, transformed DLBCL.albumin concentration lower than the limit of the normal range (LNR) before LD was.The best response to CAR-Tx and no 'bulky disease' predicted both PFS and OS.(66%) were positive for CD19 antigen.Otherwise, all the R/P histologies were the same as those of the primary samples.The characteristics of the R/P patients after CAR-Tx are summarised in Table 3.Most patients with a diagnosis other than PMBCL progressed after CAR-Tx, while only three of the 12 patients with PMBCL progressed.Fourteen patients progressed early (<1 month), 24 patients progressed within 2-3 months and 25 patients progressed >3 months after CAR-Tx.The median followup for patients with CAR T-cell survival failure at R/P after CAR-Tx was 10.6 months (range 2.4-23.2).The majority of the R/P patients had advanced-stage disease, elevated LDH, and EN involvement, and more than half of the patients had 'bulky disease' ≥5 cm and an ECOG PS >1 at progression.The persistence of A subset of the CAR Tcells was tested in a subset of the patients (n = 30), and CAR-T cells were present in more than half of the patients (n = 57%) (Table 3).
Of the 63 patients, 39 (62%) received further therapy, and 24 (38%) did not.The latter received only supportive and palliative care, mostly due to the rapidity of their progression and their poor PS.Twenty-one (87.5%) patients who did not receive further treatment had stable disease or progression as their best response after CAR-Tx, compared to 22 (56.4%) of those who received further therapy.The differences between these groups are listed in Table 4.In multivariate analysis, four risk factors for lack of further treatment were identified, three of which were present before or at the time of CAR-Tx: elevated LDH before APH, EN involvement and elevated ferritin before LD.The last risk factor was the ECOG PS at R/P status after CAR T-cell failure (Table 4).As the 1st-line treatment after R/P after CAR-Tx, six patients underwent radiotherapy (RT) and 33 patients underwent systemic therapy (excluding glucocorticoids): lenalidomide ± rituximab in seven patients, polatuzumab + bendamustine and rituximab (pola-BR) in six patients, chemotherapy ± rituximab in 15 patients, bispecific antibody in one patient, CAR T-cell reinfusion ± anti-PD1 treatment in two patients and therapy with Bruton's tyrosine kinase inhibitors in two patients.The ORR was 22% (CR 8%).The response rates after different 1st-line regimens are shown in Figure 2. Sixteen patients were further treated with 2nd-line therapy (RT in two patients, systemic therapy in 13 patients and the same second CAR T-cell product in one patient).A response was achieved in four patients (25%), one whom achieved CR.Six patients received 3rd-line therapy, one of whom received 4th-line of therapy.Bispecific antibodies (BsAbs) at any timepoint of treatment after R/P disease were indicated in six patients.In five patients, BsAbs were administered as 2nd or next-line therapy in  11-33.7],respectively).The median OS-2 was 0.2 months for patients who progressed within 1 month after CAR T-cell therapy (95% CI 0.1-3.8)and 3.2 months for patients who progressed later (95% CI 2.4-6.7).Long-term survival was not achieved in any of these patients with early R/P.The median OS-2 in treated patients was 6.7 months (6-month and 12-month OS-2: 57.9% [95% CI 42.1-73.7]and 33.1% [95% CI 16.3-49.9],respectively).For untreated patients, the median OS-2 was only 0.4 months and the median 6-month OS-2 was only 4.2% [95% CI 0-12.2](Figure 3).The median PFS-2 in treated patients was 3.2 months (95% CI 2.3-4), and the 6-month and 12-month PFS-2 in these patients 3), respectively.

| Univariate analysis and multivariate
Cox regression analysis for OS-2 in all patients who failed to respond to CAR-Tx (n = 63)

Univariate analysis and multivariate analysis for OS treated-2 and PFS treated-2 in patients who received therapy (n = 39) after CAR-Tx failure
The risk factors for PFS treated-2 and OS treated-2 according to univariate analysis and multivariate analysis are shown in Table 5.The risk factors for a shorter PFS treated-2 and OS treated-2 again included several factors presented before LD and at R/P.All factors predictive of PFS treated-2 were also predictive of OS treated-2.
In addition, LDH > LNR before LD and EN involvement at R/P predicted the OS treated-2 duration (  6-month OS treated-2 was achieved in 95% of those with 0-2 factors vs. 12% of those with ≥3 factors; median not reached vs. median = 3 months) (Figure 4).According to multivariate analysis, the risk factors for OS-2 and OS treated-2 differed.Only one factor, elevated CRP, which was present before LD, predicted OS-2 and elevated LDH before LD predicted OS treated-2.While five factors present at progression were predictive of OS-2 (SD/PD after CAR-Tx, ECOG PS > 1, decreased albumin, stage III-IV, EN involvement), only three (ECOG PS, EN involvement, albumin) predicted OS treated-2.For PFS treated-2, only CRP before LD together with ECOG PS > 1 and decreased albumin after CAR T-cell failure were predictive.

| DISCUSSION
To our knowledge, this is the first and largest real-world analysis of CAR T-cell-treated LBCL patients from Central and Eastern European countries.We retrospectively analysed 107 consecutive patients from the Czech Republic and Slovakia treated with tisa-cel or axi-cel between 2019 and 2022, with a special focus on patients whose CAR-Tx failed.8][49][50] The overall response, CR rates and median PFS and OS were also within the expected ranges.We compared the outcomes of our patients after CAR-Tx failure to those of patients in previously published studies.In their analysis of 238 patients, di Blasi et al. 51 reported a median OS-2 of 5.2 months and a PFS-2 of 2.8 months for all failed patients, 65% of whom received further treatment.In two 2023 studies, Zurko et al. 52 reported a median PFS treated-2 of 2.8 months and a median OS-2 5.5 months, while Alacron et al. 53 reported a median EFS-2 of 1.9 months and a median OS treated-2 of 8.5 months.2][53][54][55][56] We chose slightly different methods of data reporting, stressing the importance of both OS-2 and OS treated-2, and we reported PFS after CAR-Tx failure only for patients who received further treatment (PFS treated-2).We believe this makes sense, as it is sometimes difficult to determine the date of progression in untreated patients.In contrast to our study, other authors also did not mention the risk for not receiving treatment.Among our patients who received further treatment after CAR T-cell failure, the response rates to the 1st-line treatment were low.With the exclusion of regimen polatuzumab-bendamustine and rituximab (pola-BR), which was analysed separately, most patients were treated with immunochemotherapy (n = 15, ORR 15%, CR 0%).These results are worse than those of Zurko et al. 52,56 (n = 17, ORR 35%, CR 12%) but better than those of di Blasi et al. 51 (n = 31, ORR 8%, CR 4%).As in our study, no CR after immunochemotherapy was observed by Alarcon et al. (n = 15 patients). 53The finding that conventional immunochemotherapy is an ineffective treatment after CAR-Tx failure was also confirmed by Nastoupil et al. 55 in 2023 (n = 43 patients, ORR 14%, CR 7%).Pola-BR, on the contrary, was an effective salvage regimen in our cohort, where five of six patients responded (with CR in four patients).One patient who was consolidated with autologous stem cell transplantation (autoSCT) progressed early after transplantation.Only one of four patients received bispecific antibodies (BsAbs) as a first-line treatment after CAR-Tx failure.That one patient achieved PR, while three of five patients receiving BsAbs as a next-line treatment responded (one achieved CR, two achieved PR).
Factors predicting the ability to receive treatment after R/P or survival in our cohort may be divided into patientrelated factors (ECOG PS, inflammatory status) and disease-related factors (extent of the disease, LDH [indirectly tumour burden], tumour intrinsic factors).
Most of the factors predicting the probability of further treatment according to multivariate analysis were already present at APH and before LD and consisted of two disease-related factors (EN involvement and LDH) and one inflammatory factor (ferritin).The ECOG PS at R/P was an additional prognostic factor.As the probability of receiving further treatment at R/P affects further survival, patients with the abovementioned pretreatment characteristics deserve special attention.Factors for not receiving further treatment in R/P patients were mostly different from factors predicting OS treated-2 or PFS treated-2 in failed patients who received further treatment, but again, two factors measured before treatment (CRP and LDH before LD) predicted OS treated-2 and CRP before LD for PFS treated-2 as well.Again, simple measurement of these two laboratory markers may draw closer attention to subsets of ultrahigh-risk patients.Three other factors for the survival of treated patients who failed to respond (low albumin concentration, ECOG PS and EN involvement) were present at R/P.Even if we have early knowledge of parameters influencing outcomes, it is difficult to address them properly.Currently, we are unable to address parameters of inflammation, so we must focus on improving disease-related factors and poor performance status.'Bulky disease' (≥5 cm, predictive of survival), LDH and EN involvement (predictive for not receiving treatment after CAR-Tx R/P) may be addressed by bridging therapy.'Lymphoma debulking' before CAR-Tx has a confirmed role, 21,26,27,41,57,58 and it may also improve performance status, but too aggressive bridging may in fact worsen this parameter and negatively impact survival outcomes.
0][61][62][63] Bispecifics targeting different antigens are effective after CAR T-cell failure, and in a retrospective analysis using a matched control cohort from the French registry, prior treatment with BsAbs did not reduce the effect of CAR-Tx. 64,65These therapies may be successful, not only when overt progression occurs.It would be of interest whether a short course of BsAbs alone or in combination with chemotherapy might be used for 'bridging' or whether patients achieving only partial remission on BsAbs monotherapy might be successfully consolidated by CAR-Tx.Another tool that may prevent deterioration of ECOG PS and progression of disease before CAR-Tx is shortening CAR T-cell production. 66loser follow-up after treatment should also be employed.Currently, the first PET/CT scan is recommended as early as 1 month after CAR T-cell infusion, but the possibility of an even earlier assessment of response needs to be examined.The inclusion of minimal residual disease monitoring (MRD) by noninvasive circulating tumour (ct) DNA analysis could improve prognostication beyond PET/CT.In two studies, ctDNA assessments were used to predict the outcome of patients receiving axi-cel or tisa-cel for LBCL therapy. 67,68enalidomide maintenance was used with some success in patients with early evidence of treatment failure or in only partial remission after CAR-Tx.Patients who achieve a PR after CAR-Tx should be seriously considered for next-line treatment and possibly for allogeneic SCT.63][69][70][71][72] Despite its multicentre nature, our study has several limitations.First, this was a retrospective analysis.Second, we treated the patients with two different CAR Tcell products.Third, the group of failing patients was relatively small, and their choice of individual therapy options might be biased by patient and physician preferences, as well as by reimbursement issues.
In summary, our retrospective study confirmed the unfavourable prognosis of patients with LBCL who progressed or relapsed after treatment with the commercially available CAR T-cell products tisa-cel and axi-cel.We confirmed the limited role of salvage immunochemotherapy, with the possible exception of the pola-BR regimen.BsAbs were relatively effective even when used in later lines of treatment after CAR-Tx failure.We identified prognostic factors for progression after CAR-Tx, for the ability to receive further treatment, and for outcomes after progression in untreated and treated patients.We found that several factors predictive of the R/P ratio after CAR-Tx, the probability of further treatment, and the outcome after relapse were present even before the patients started CAR T-cell infusion.These findings can form a basis for further refinement of the management of CAR T-cell therapy, enabling the identification of an ultrahigh-risk subgroup of CAR T-cell candidates who may benefit from aggressive pre-CAR T-cell therapy ('debulking').Early evaluation of the response after CAR-Tx is needed to address CAR-Tx failure (early MRD monitoring, early restaging [CT/PET] after CAR-Tx).When only a PR is achieved after CAR-Tx, early intervention is appropriate due to the high risk of CAR-Tx failure.

| CONCLUSION
To prevent R/P disease after CAR-Tx and reduce the number of patients who cannot receive treatment after eventual R/P, we need to address the ECOG PS and systemic inflammatory status of patients during the indication process and consider appropriate lymphoma debulking strategies before CAR-Tx.To give more relapsing patients the opportunity for further treatment, early evaluation of the treatment response is necessary, ideally with the inclusion of ctDNA-MRD monitoring when it becomes available.The incorporation of BsAbs into bridging therapy or early after R/P should be investigated.Finally, better understanding of CAR T-cell resistance and the development of new CAR T-cell products and strategies will increase the efficacy of this treatment modality and hopefully reduce the number of failed LBCL patients in the future.
Funding information grant AZV NU21-03-00411 from the Ministry of Health of the Czech Republic, Grant/Award Number: NU21-03-00411; This work was supported by the Ministry of Health, Czech Republic under grant MH CZ-DRO (UHHK, 00179906), under grant AZV NU21-03-00411 and by Charles University in Prague under the Cooperatio program, research area "Oncology and Haematology".

3. 1 . 4 |
Treatment, response to treatment and clinical outcome after CAR T-cell failure

F I G U R E 4
Progression-free survival (PFS treated-2;A) and overall survival (OS treated-2; B) of patients who failed to respond to CAR T-cell therapy (n = 39).Albumin < LNR at relapse/progression (R/P)ECOG PS >1 at risk factors, 6month PFS-2 37% risk factors p<0.0001Risk factors: LDH > LNR before (LD) CRP > LNR before LD < LNR at relapse/progression (R/P) ECOG PS > 1 at R/P EN involvement at R/P p<0.00001 risk factors, 6month OS-2 95% risk factors, 6month OS-2 12% Baseline comparison of patients in durable remission and those with CAR T-cell failure.
T A B L E 1 3.1.3|FailureafterCAR-Tx At the time of analysis, 63 patients had failed CAR-Tx.The differences in characteristics before or at the time of CAR-Tx between patients with long-term durable CR and patients with R/P DLBCL are summarised in Table1.Patients at the time of APH were older than patients without CAR T-cell failure, and their haemoglobin and albumin levels before LD were more frequently below the respective LNRs.Repeat tumour biopsy was performed in 18 patients (29%) after CAR T-cell failure, and 12 patients F I G U R E 1 Progression-free survival (n = 107).T A B L E 2 Univariate analysis and multivariate analysis for overall survival (OS) and progression-free survival (PFS) (n = 107).Abbreviations: CAR, chimeric antigen receptor; CAR-T, chimeric antigen receptor; CI, confidence interval; ECOG PS, Eastern Cooperative Oncology Group Performance Status; EN, extranodal; LDH, lactate dehydrogenase; LDH, lactate dehydrogenase; LNR, limit of normal; n, number.;PD, progressive disease; PMBCL, primary mediastinal B-cell lymphoma; SD, stable disease; SD/PD, stable disease/progression.
Baseline characteristics of the patients at relapse/ progression after CAR T-cell therapy (n = 63).
T A B L E 3Abbreviations: AA IPI age-adjusted IPI; CAR, chimeric antigen receptor; CNS, central nervous system; DLBCL, diffuse large B, cell lymphoma; ECOG PS, Eastern Cooperative Oncology Group Performance Status; EN, extranodal; HGBCL, high grade B-cell lymphoma; IPI, International Prognostic Index; LDH, lactate dehydrogenase; LNR, limit of normal range; n, number; NA, not available; PMBCL, primary mediastinal B, cell lymphoma; tDLBCL, transformed DLBCL.three patients (CR in one patient, PR in two patients).
Baseline characteristics of the analysed patients who experienced relapse/progression after CAR T-cell therapy (n = 63).
T A B L E 5